Regulation of interleukin IL-4, IL-13, IL-10, and their downstream components in lipopolysaccharide-exposed rat lungs. Comparison of the constitutive expression between rats and humans

Interleukin (IL)-4, IL-10, and IL-13 are T-helper2 cell derived cytokines, which are known to suppress pro-inflammatory cytokine production. The biologically related IL-4 and IL-13 have an impact on the development of atopic inflammation, whereas IL-10 is mostly supposed to be involved in fibrotic disorders or inflammatory bowel disease. Their influence on the pathogenesis of severe lung injury is widely unknown. The expression of these proteins is mostly assumed to be restricted to leukocytic cells. Recently, some non-leukocytic cell types have been described to generate these mediators. In the present study, the constitutive cellular distribution pattern of IL-4, IL-13, IL-10, IL-4R alpha, STAT6 and IL-10R was elaborated by immunohistochemistry in the rat organism. Cytokine-specific regulation in lipopolysaccharide (LPS)-challenged rat lungs was investigated and constitutive expression was compared with human lungs. The study demonstrates strong expression of IL-4, IL-10, and IL-13 in different non-leukocytic cell types, especially in endothelial and epithelial cells in the entire rat organism. In concert with rat lung expression human lungs show strong similarities. Moreover, vascular LPS challenge of rat lungs generally demonstrates cell type-specific downregulation of the cytokines. We conclude that non-leukocytic cells in the organism play an important role in the regulation of organ-specific inflammatory reactions, especially in lungs.